The diseases collectively known as periodontitis are bacterial infections. A small group of gram-negative oral bacteria are consistently associated with specific forms of disease. The presence of P. gingivalis is linked to chronic and severe adult periodontitis. P. gingivalis and the other periodontal pathogens are observed within diseased human gingiva, but the molecular mechanisms of attachment to, and penetration of, tissue are unknown. Previously, the applicant demonstrated, with quantitative data, that P. gingivalis attached to and invaded oral epithelial cells. A subsequent study showed that this organism was able to penetrate and divide within the cells of a multilayered pocket epithelium model. The current goal is to dissect the molecular events in the initial interactions between the bacterium and epithelial cells. This application focuses on the molecular mechanisms of attachment of P. gingivalis to epithelial cells. New data are presented on the in vitro modulation of attachment using P. gingivalis wild type and mutant strains. Data is also presented on P. gingivalis genes isolated after screening an expression library for clones which bound epithelial cells. The specific aims of this application are to: 1) determine the P. gingivalis activities required for attachment to epithelial cells in vitro; 2) identify the bacterial genes involved in attachment; and 3) isolate P. gingivalis isogenic mutants defective in these genes. The cross-talk between P. gingivalis and the epithelial cell takes place at the attachment step, and the infection pathway is decided, in part, by the signaling between the two cell types. Therefore, attachment is the key target for preventative intervention strategies and understanding the molecular mechanisms of attachment is critical for the development of successful therapies.